Correcting Circadian Rhythms to Breakthrough in Bipolar Disorder

NCT06226025 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: HUM002357781R21MH132901-01A1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test whether a dietary supplement (low-dose melatonin) commonly used to treat night owls, administered in conjunction with a behavioral sleep intervention, will help to shift the brain clock earlier and improve mood and sleep in bipolar disorder. Eligible participants will be randomized to receive melatonin plus a behavioral sleep intervention or placebo plus a behavioral sleep placebo. The hypotheses for this study include:

• Melatonin plus behavioral sleep intervention (compared to placebo plus behavioral sleep placebo) will produce a greater advance of dim light melatonin onset (DLMO), between pre- and post-treatment.
• Melatonin (compared to placebo) will produce a greater reduction in Patient Health Questionnaire-9 score between pre- and post-treatment.

Conditions

Bipolar Disorder; Delayed Sleep-Wake Phase Disorder

Keywords

Correcting Circadian Rhythms; Melatonin; Placebo; Dim light melatonin onset

Outcome Measures

Primary Outcomes (1)

• Change in time of Dim Light Melatonin Onset (DLMO) baseline (pre-treatment) to 4 weeks (post-treatment)

  Onset of melatonin in dim light conditions as measured in saliva (also called DLMO). Time of DLMO is measured in clock time and change in time of DLMO is measured in hours. The change score is calculated as time at 4 weeks minus baseline time. Thus, positive scores indicate a shift towards a later onset of melatonin and negative scores indicate a shift towards an earlier onset of melatonin.

  4 weeks (after treatment period)

Secondary Outcomes (1)

• Change in the Patient Health Questionnaire-9 (PHQ-9)

  Baseline, 4 weeks (after treatment period)

Study Arms (2)

Melatonin

EXPERIMENTAL

Oral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period.

Drug: Melatonin; Behavioral: Behavioral sleep intervention

Placebo

PLACEBO COMPARATOR

Oral medication will be taken for 28 days on the afternoon or evening of the participants first intervention session and continue daily for the remainder of the treatment period.

Other: Placebo; Behavioral: Behavioral sleep control

Interventions

Melatonin DRUG

Participants randomized to this intervention will take 1 oral pill (0.5 milligrams (mg)) daily. They will attend 4 weekly behavioral sleep intervention sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device.

Melatonin

Placebo OTHER

Participants randomized to this intervention will take 1 oral placebo pill daily. They will attend 4 weekly behavioral sleep control sessions with a therapist. In addition, participants will complete questionnaires (MyDataHelp app), monitor sleep, collect saliva samples, and wear the Fitbit Device.

Placebo

Behavioral sleep intervention BEHAVIORAL

An active intervention that is typically paired with melatonin to maximize treatment effects.

Melatonin

Behavioral sleep control BEHAVIORAL

A behavioral placebo (which does not improve sleep in delayed sleep-wake phase disorder) to control for social/interpersonal effects of behavioral sleep intervention sessions.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Capable of giving informed consent
• Meet The Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for bipolar disorder (BD) I or II
• Evening chronotype per the Morningness-Eveningness Questionnaire (MEQ) defined by a score of \<42
• At least mild depressive symptoms on the Patient Health Questionnaire (PHQ)-9 defined by a score ≥5
• Psychotropic medications at stable dose for past month
• Able to download the MyDataHelps mobile application (app), and open app on participants' own phone
• Willing to abstain from alcohol for the duration of the intervention phase
• Female participants of childbearing potential (i.e., patients are not permanently sterilized (hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or postmenopausal (12 months with no menses without an alternative medical cause) by report) must agree to use a reliable method of contraception from the screening visit until 4 weeks after the study has completed.

You may not qualify if:

• Current diagnosis of, or high risk for, a sleep disorder other than DSPD per interview and medical record review (when available) including:
• Insomnia per DSM-5
• Sleep-disordered breathing per Snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender (STOP-BANG)
• Restless leg syndrome per sleep interview
• Narcolepsy
• Suspicion of vasomotor symptoms impacting sleep per interview for women that may be perimenopausal or postmenopausal.
• Risk of current mania (per Young Mania Rating Scale (YMRS) score \> 19).
• Suicidal or at high risk for suicide per Columbia Suicide Severity Rating Scale (C-SSRS) guidelines (i.e., presence of any suicidal behavior-suicide attempt, interrupted attempt, abort attempt, or preparatory behavior-in the past 3 months; and/or current active suicidal ideation with any intent), or as determined by the principal investigators.
• Presence of cardiac implantable electronic device, such as defibrillator or pacemaker.
• Presence of chronic psychiatric conditions which may directly influence sleep per interview and medical record review (when available), including:
• Current illicit drug use per the Drug Use Disorders Identification Test (DUDIT) defined by a score of ≥ 25
• Current alcohol or drug abuse per the Alcohol Use Disorder Identification Test (AUDIT) defined by a score of ≥ 16 and DUDIT
• Currently experiencing psychosis
• Presence of unstable chronic medical condition which may directly influence sleep:
• Chronic pain

Sponsors & Collaborators

• Leslie Swanson: lead
• University of Michigan: collaborator
• Natrol: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

MeSH Terms

Conditions

Bipolar Disorder; Sleep Disorders, Circadian Rhythm

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Chronobiology Disorders; Nervous System Diseases; Dyssomnias; Sleep Wake Disorders; Occupational Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Leslie Swanson, PhD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelley DuBuc

CONTACT

734-764-2256; dubuck@umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Model Details: Participants that meet eligibility for the randomized trial are randomized using minimization in a 1:1 ratio to low-dose afternoon melatonin plus a behavioral sleep intervention (MEL) or placebo tablet plus behavioral sleep placebo (CTL)

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 26, 2024
• Study Start: August 13, 2024
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)